Clinical Trial Page

Summary
EudraCT Number:2021-006326-48
Sponsor's Protocol Code Number:CO43810
National Competent Authority:Spain - AEMPS
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-06-15
Trial results
A. Protocol Information
A.1Member State ConcernedSpain - AEMPS
A.2EudraCT number2021-006326-48
A.3Full title of the trial
A PHASE I/II, OPEN-LABEL, SINGLE-ARM, TWO-PART TRIAL TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI-TUMOR ACTIVITY OF GLOFITAMAB IN COMBINATION WITH CHEMOIMMUNOTHERAPY IN PEDIATRIC AND YOUNG ADULT PARTICIPANTS WITH RELAPSED/REFRACTORY MATURE B-CELL NON-HODGKIN LYMPHOMA
ENSAYO DE FASE I/II, ABIERTO, DE UN SOLO GRUPO Y DOS PARTES PARA EVALUAR LA SEGURIDAD, TOLERABILIDAD, FARMACOCINÉTICA Y ACTIVIDAD ANTITUMORAL DE GLOFITAMAB EN COMBINACIÓN CON QUIMIOINMUNOTERAPIA EN PARTICIPANTES PEDIÁTRICOS Y ADULTOS JÓVENES CON LINFOMA NO HODGKIN DE CÉLULAS B MADURAS EN RECAÍDA O REFRACTARIO
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Combination with Chemoimmunotherapy in Pediatric and Young Adult Participants with Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
Estudio para Evaluar la Seguridad, Tolerabilidad, Farmacocinética y Actividad Antitumoral de Glofitamab en Combinación con Quimioinmunoterapia en Participantes Pediátricos y Adultos Jóvenes con Linfoma No Hodgkin De Células B Maduras en Recaída o Refractario
A.4.1Sponsor's protocol code numberCO43810
A.7Trial is part of a Paediatric Investigation Plan Yes
A.8EMA Decision number of Paediatric Investigation PlanP/094/2020
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorRoche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
B.1.3.4CountrySwitzerland
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportF. Hoffmann-La Roche Ltd
B.4.2CountrySwitzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationF.Hoffmann-La Roche Ltd
B.5.2Functional name of contact pointTrial Information Support Line-TISL
B.5.3 Address:
B.5.3.1Street AddressGrenzacherstrasse 124
B.5.3.2Town/ cityBasel
B.5.3.3Post code4070
B.5.3.4CountrySwitzerland
B.5.4Telephone number+34913257300
B.5.5Fax number+34913248196
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
D.2.5.1Orphan drug designation numberEU/3/21/2497
D.3 Description of the IMP
D.3.1Product nameGlofitamab
D.3.2Product code RO7082859/F04-01
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNGlofitamab
D.3.9.2Current sponsor codeRO7082859
D.3.9.4EV Substance CodeSUB197235
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number1
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Gazyvaro
D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameObinutuzumab
D.3.2Product code RO5072759
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNObinutuzumab
D.3.9.1CAS number 949142-50-1
D.3.9.2Current sponsor codeRO5072759
D.3.9.3Other descriptive nameOBINUTUZUMAB/ GA101
D.3.9.4EV Substance CodeSUB32751
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 3
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name MabThera
D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameRituximab
D.3.2Product code RO0452294/V02-02
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNRituximab
D.3.9.1CAS number 174722-31-7
D.3.9.2Current sponsor codeRO0452294
D.3.9.4EV Substance CodeSUB12570MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number10
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product Yes
D.3.11.13.1Other medicinal product typeRecombinant humanized monoclonal antibody
D.IMP: 4
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Actemra®/RoActemra®
D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameTocilizumab
D.3.2Product code RO4877533/F01-02
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNTocilizumab
D.3.9.1CAS number 375823-41-9
D.3.9.3Other descriptive nameTOCILIZUMAB
D.3.9.4EV Substance CodeSUB20313
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number20
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 5
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name IFO-cell® N 2000 Solution for Infusion
D.2.1.1.2Name of the Marketing Authorisation holderSTADAPHARM GmbH
D.2.1.2Country which granted the Marketing AuthorisationGermany
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameIfosfamide
D.3.4Pharmaceutical form Solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNIfosfamide
D.3.9.1CAS number 3778-73-2
D.3.9.3Other descriptive nameIFOSFAMIDE
D.3.9.4EV Substance CodeSUB08125MIG
D.3.10 Strength
D.3.10.1Concentration unit g/ml gram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number0.04
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 6
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name CARBOPLATIN ACCORD 10 mg/ml solution for infusion
D.2.1.1.2Name of the Marketing Authorisation holderACCORD HEALTHCARE FRANCE SAS
D.2.1.2Country which granted the Marketing AuthorisationFrance
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameCarboplatin
D.3.4Pharmaceutical form Solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNCarboplatin
D.3.9.3Other descriptive nameCARBOPLATIN
D.3.9.4EV Substance CodeSUB06614MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number10
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 7
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name ETOPOSIDE ACCORD 20 mg/mL concentrate for solution for infusion
D.2.1.1.2Name of the Marketing Authorisation holderACCORD HEALTHCARE FRANCE SAS
D.2.1.2Country which granted the Marketing AuthorisationFrance
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameEtoposide
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNEtoposide
D.3.9.3Other descriptive nameETOPOSIDE
D.3.9.4EV Substance CodeSUB07337MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number20
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
CD20 positive B-Cell Non-Hodgkin Lymphoma
Linfoma No Hodgkin de Células B CD20 positivo
E.1.1.1Medical condition in easily understood language
Non-Hodgkin's lymphoma is a type of cancer that begins in your lymphatic system, which is part of the body's germ-fighting immune system.
Linfoma No Hodgkin es un tipo de cáncer que comienza en el sistema linfático, que es parte del sistema inmunológico del cuerpo que combate los gérmenes
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 23.1
E.1.2Level LLT
E.1.2Classification code 10084346
E.1.2Term B-cell non-Hodgkin's lymphoma
E.1.2System Organ Class 100000004864
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
● To evaluate the efficacy of glofitamab in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) chemoimmunotherapy, as assessed by the investigator based on achievement of a complete response (CR)
● To evaluate the safety and tolerability of glofitamab in combination with R-ICE chemoimmunotherapy
● To determine the pharmacokinetics of glofitamab alone and in combination with R-ICE chemoimmunotherapy
-Evaluar la eficacia de glofitamab en combinación con quimioinmunoterapia con rituximab, ifosfamida, carboplatino y etopósido (R-ICE), según la evaluación del investigador basado en la consecución de una respuesta completa (RC).
- Evaluar la seguridad y la tolerabilidad de glofitamab en combinación con quimioinmunoterapia con R-ICE
- Determinar la farmacocinética de glofitamab en monoterapia y en combinación con quimioinmunoterapia con R-ICE.
E.2.2Secondary objectives of the trial
● To evaluate the anti-tumor activity of glofitamab in combination with R-ICE chemoimmunotherapy and glofitamab monotherapy
● To evaluate the safety and tolerability of glofitamab monotherapy
● To determine the pharmacokinetics of obinutuzumab and rituximab
● To evaluate the immune response to glofitamab
-Evaluar la actividad antitumoral de glofitamab en combinación con quimioinmunoterapia con R-ICE y de glofitamab en monoterapia
-Evaluar la seguridad y la tolerabilidad de glofitamab en monoterapia.
-Determinar la farmacocinética de obinutuzumab y rituximab.
-Evaluar la respuesta inmunitaria a glofitamab.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
● Age 6 months to <18 years at the time of signing Informed Consent for Part 1 and Cohort B of the study, and age 6 months to <=30 years old at the time of signing Informed Consent for Part 2 of the study
● Histologically re-confirmed diagnosis prior to study entry of aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) that expresses CD20 (reconfirmed by immunohistochemistry [IHC]), including Burkitt lymphoma (BL), Burkitt leukemia (BAL) (mature B-cell leukemia fragment antigen-binding [FAB] L3), diffuse large B-cell lymphoma (DLBCL), and primary mediastinal large B-cell lymphoma (PMBCL), at the time of first relapsed or refractory (R/R) disease for Cohort A and second or greater R/R disease for Cohort B
● Refractory or relapsed disease following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens for Cohort B
● Measurable disease
● Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales
● Adequate bone marrow function
● Adequate liver and renal function
● Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
● Negative test results for hepatitis C virus (HCV) and HIV
● For female participants of childbearing potential, or who will reach childbearing potential during the study: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 18 months after obinutuzumab pretreatment, 2 months after the final dose of glofitamab, 12 months after the final dose of rituximab and/or ifosfamide, carboplatin, and etoposide (ICE), or 3 months after the final dose of tocilizumab
● For male participants who are expected to reach sexual maturity during the study, or have already reached sexual maturity by the screening visit: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 3 months after pretreatment with obinutuzumab, 2 months after the final dose of glofitamab, 6 months after the final dose of rituximab and/or ICE, or 2 months after the last dose of tocilizumab (if applicable), whichever is longer, to avoid exposing the embryo
● Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods
-Edad de 6 meses a < 18 años en el momento de firmar el consentimiento informado para la parte 1 y la cohorte B del estudio y edad de 6 meses a <= 30 años en el momento de firmar el consentimiento informado para la parte 2 del estudio
-Diagnóstico reconfirmado histológicamente antes de la entrada en el estudio de LNH-B (linfoma no hodgkin de células B) maduro agresivo que expresa CD20 (reconfirmado mediante inmunohistoquímica), incluidos LB (linfoma de Burkitt), LAB (leucemia de Burkitt; leucemia de linfocitos B maduros FAB L3), LDCBG (linfoma difuso de células B grandes) y LMPLB (linfoma mediastínico primario de células B grandes), en el momento de la primera enfermedad R/R en la cohorte A y la segunda enfermedad R/R o posterior en la cohorte B.
-Enfermedad refractaria o en recaída después de la quimioinmunoterapia habitual de primera línea en la cohorte A y después de al menos dos pautas previas de quimioinmunoterapia sistémica en la cohorte B
-Enfermedad mensurable
- Estado funcional adecuado, evaluado conforme a las escalas del estado funcional de Lansky o Karnofsky
- Función medular adecuada
- Función hepática adecuada
- Resultados negativos en las pruebas serológicas o de reacción en cadena de la polimerasa (PCR) para la infección aguda o crónica por el virus de la hepatitis B (VHB).
- Resultados negativos en el análisis del virus de la hepatitis C (VHC) y VIH
-Mujeres con capacidad de procrear o que vayan a alcanzar la capacidad de procrear durante el estudio: compromiso de practicar la abstinencia sexual (no mantener relaciones heterosexuales) o de utilizar métodos anticonceptivos durante el período de tratamiento y durante al menos 18 meses después del pretratamiento con obinutuzumab, 2 meses después de la última dosis de glofitamab, 12 meses después de la última dosis de rituximab y/o ICE (ifosfamida, carboplatino y etopósido) o 3 meses después de la última dosis de tocilizumab (si procede), lo que suponga más tiempo.
-Varones que se espera que alcancen la madurez sexual durante el estudio o que ya la hayan alcanzado en la visita de selección: compromiso de practicar la abstinencia sexual (abstenerse de mantener relaciones heterosexuales) o de utilizar preservativo y compromiso de abstenerse de donar semen durante el período de tratamiento y durante al menos 3 meses después del pretratamiento con obinutuzumab, 2 meses después de la última dosis de glofitamab, 6 meses después de la última dosis de rituximab y/o ICE o 2 meses después de la última dosis de tocilizumab (si procede), lo que suponga más tiempo, para evitar la exposición del embrión
- Participantes y/o cuidadores que estén dispuestos y sean capaces de realizar las evaluaciones de resultados clínicos durante todo el estudio, bien sea en papel o con un entrevistador
E.4Principal exclusion criteria
● Isolated CNS disease of mature B-NHL without systemic involvement, and primary central nervous system (CNS) lymphoma
● Receipt of glofitamab prior to study enrollment
● Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade <=1
● Grade >=3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
● Prior solid organ transplantation
● Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
● Known or suspected chronic active Epstein-Barr viral infection (CAEBV)
● Active autoimmune disease requiring treatment
● History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
● History of confirmed progressive multifocal leukoencephalopathy
● Current or past history of uncontrolled non-malignant CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
● Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
● Major surgery or significant traumatic injury <28 days prior to the obinutuzumab pretreatment infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
● Administration of a live, attenuated vaccine within 4 weeks before the start of study treatment (obinutuzumab pretreatment) or at any time during the study treatment period and within 12 months after end of study treatment
● Participants with any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
● Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Exclusion criteria applicable to Cohort A only
● Receipt of any R-ICE chemoimmunotherapy prior to study enrollment into Cohort A
● Receipt of more than one prior line of standard-of-care B-NHL chemoimmunotherapy
● Prior allogeneic or autologous stem cell transplantation (SCT)
Exclusion criteria applicable to Cohort B only
● Prior treatment with systemic chemotherapy and immunotherapeutic agents
● Patients with uncontrolled CNS involvement
● Prior allogeneic or autologous SCT <=100 days post-transplant prior to enrollment
● Presence of Grade >=2 acute or extensive chronic graft -versus-host disease (GVHD) in participants who received prior allogeneic hematopoietic stem cell transplantation (HSCT)
- Enfermedad aislada del SNC por el LNH-B maduro sin afectación sistémica y linfoma primario del SNC.
-Tratamiento con glofitamab antes de la inclusión en el estudio.
-Acontecimientos adversos persistentes desde el tratamiento antineoplásico previo que no se hayan resuelto a un grado <= 1.
- Acontecimientos adversos de grado  3, a excepción de endocrinopatía de grado 3 controlada con tratamiento de reposición.
-Trasplante previo de órgano sólido.
-Antecedentes confirmados o sospecha de linfohistiocitosis hemofagocítica (LHH).
-Confirmación o sospecha de infección activa crónica por el virus de Epstein-Barr.
- Enfermedad autoinmunitaria activa con necesidad de tratamiento.
-Antecedentes de reacciones alérgicas o anafilácticas graves al tratamiento con anticuerpos monoclonales (o proteínas de fusión relacionadas con anticuerpos recombinantes) o sensibilidad o alergia conocidas a productos de origen murino
-Antecedentes de leucoencefalopatía multifocal progresiva confirmada.
-Presencia o antecedentes de enfermedad del SNC no maligna que no esté controlada, como ictus, epilepsia, vasculitis del SNC o enfermedad neurodegenerativa
-Signos de enfermedades concomitantes importantes y no controladas que puedan afectar al cumplimiento del protocolo o a la interpretación de los resultados.
-Intervención de cirugía mayor o traumatismo importante < en los 28 días previos a la infusión de pretratamiento con obinutuzumab (excluidas las biopsias) o previsión de que sea necesaria una intervención de cirugía mayor durante el tratamiento del estudio.
-Administración de una vacuna de microorganismos vivos atenuados en las 4 semanas previas al comienzo del tratamiento del estudio (pretratamiento con obinutuzumab) o en cualquier momento durante el período de tratamiento del estudio y en los 12 meses siguientes al final del tratamiento del estudio.
-Participantes con cualquier otra enfermedad, disfunción metabólica, hallazgo en la exploración física o resultado en los análisis clínicos que haga sospechar de forma razonable una enfermedad o proceso que podría contraindicar el uso de un fármaco en investigación.
-Embarazo o lactancia, o intención de quedarse embarazada durante el estudio
Criterios de exclusión aplicables únicamente a la cohorte A
- Recepción de cualquier quimioinmunoterapia con R-ICE antes de la inclusión en la cohorte A del estudio
-Recepción de más de una línea previa de quimioinmunoterapia habitual para el LNH-B.
-Alotrasplante o autotrasplante de células progenitoras previo.
Criterios de exclusión aplicables únicamente a la cohorte B
-Tratamiento previo con quimioterapia sistémica e inmunoterápicos
- Se excluirá a los pacientes con afectación del SNC no controlada
- Trasplante alogénico o autólogo de células progenitoras previo si han transcurrido  100 días después del trasplante y antes de la inclusión
-Presencia de enfermedad del injerto contra el huésped (EICH) crónica aguda o extensa de grado >= 2 en participantes que hayan recibido un alo-TCPH previo.
E.5 End points
E.5.1Primary end point(s)
1. Achievement of a complete response (CR) after up to three cycles of treatment as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants (glofitamab plus R-ICE chemoimmunotherapy)
2. Incidence, nature, frequency, severity, and timing of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0) (glofitamab plus R-ICE chemoimmunotherapy)
3. Change from baseline in physical findings, vital signs, clinical laboratory test results and electrocardiogram (ECG) (glofitamab plus R-ICE chemoimmunotherapy)
4. Pharmacokinetics (PK) parameters (as appropriate) and serum concentrations of glofitamab monotherapy at specified timepoints
5. PK parameters (as appropriate) and serum concentrations of glofitamab in combination with R-ICE chemoimmunotherapy at specified timepoints
1. Consecución de una RC después de un máximo de tres ciclos de tratamiento, según lo determinado por el investigador conforme a los Criterios internacionales de respuesta del LNH pediátrico para participantes pediátricos y la Clasificación de Lugano para participantes adultos jóvenes (glofitamab con quimioinmunoterapia con R-ICE)
2. Incidencia, naturaleza, frecuencia, gravedad y cronología de los acontecimientos adversos, con determinación de la gravedad conforme a los Criterios terminológicos comunes para acontecimientos adversos, version 5 (CTCAE del NCI, v5.0.) (glofitamab con quimioinmunoterapia con R-ICE).
3. Variación con respecto al momento basal de los resultados de la exploración física, constantes vitales, resultados analíticos de laboratorio y electrocardiográficos (ECG) (glofitamab con quimioinmunoterapia con R-ICE).
4. Parámetros farmacocinéticos (según proceda) y concentraciones séricas de glofitamab en monoterapia en puntos temporales especificados.
5. Parámetros farmacocinéticos (según proceda) y concentraciones séricas de glofitamab en combinación con quimioinmunoterapia R-ICE en puntos temporales especificados.
E.5.1.1Timepoint(s) of evaluation of this end point
1. Up to 9 weeks
2. Up to approximately 1 year
3. Baseline to 1 year
4. At Days 1, 8, 15 of Cycle 1; Day 1 of each cycle from Cycle 2 and end of treatment (EOT)
5. At Days 1, 8, 15 of Cycle 1; Day 1 of Cycle 2; Days 1, 5 of Cycle 3 and at EOT
1. Hasta 9 semanas
2. Hasta aproximadamente 1 año
3. Desde momento basal a 1 año
4. En los días 1, 8, 15 de Ciclo 1; Día 1 de cada ciclo desde el Ciclo 2 y final de tratamiento (EOT)
5. En los días 1, 8, 15 de Ciclo 1; Día 1 de Ciclo 2; Días 1, 5 de Ciclo 3 y al EOT
E.5.2Secondary end point(s)
1. For glofitamab plus R-ICE chemoimmunotherapy: Objective response rate (ORR), Duration of complete response (DOCR), Progression-free survival (PFS) after enrollment, Event-free survival (EFS), Overall survival (OS) and percentage of patients who proceed to HSCT after up to three cycles of treatment
2. For glofitamab monotherapy: ORR, Duration of response (DOR) and OS
3. Incidence, nature, frequency, severity, and timing of adverse events, with severity determined according to NCI CTCAE v5.0 (glofitamab monotherapy)
4. Change from baseline in physical findings, vital signs, clinical laboratory test results and ECG (glofitamab monotherapy)
5. Serum concentrations of obinutuzumab at specified timepoints
6. Serum concentrations of rituximab at specified timepoints
7. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs against glofitamab during the study
. Para glofitamab en combinación con quimioinmunoterapia con R-ICE: Tasa de respuesta objetiva (TRO), duración de la respuesta completa (DRC), supervivencia libre de progresión (SLP) después de la ramdomización, supervivencia sin acontecimientos (SSA), Supervivencia global (SG) yPorcentaje de pacientes que se someten a TCMH después de un máximo de tres ciclos de tratamiento
2. Para glofitamab en monoterapia: TRO), duración de la respuesta (DR) y SG
3. Incidencia, naturaleza, frecuencia, gravedad y cronología de los acontecimientos adversos, con determinación de la gravedad conforme a los criterios CTCAE del NCI, v5.0 (glofitamab en monoterapia).
4. Variación con respecto al momento basal de la exploración física, constantes vitales, resultados analíticos de laboratorio y ECG (glofitamab en monoterapia)
5. Concentraciones séricas de obinutuzumab en puntos temporales especificados.
6. Concentraciones séricas de rituximab en puntos temporales especificados.
7. Prevalencia de ACF en el momento basal e incidencia de ACF durante el estudio
E.5.2.1Timepoint(s) of evaluation of this end point
1-3. Up to approximately 1 year
4. Baseline to 1 year
5. At Days 1, 8, 15 of Cycle 1
6. At Days 1, 5 of Cycle 3
7. At Days 1, 8 of Cycle 1; At Day 5 of Cycle 3 and at EOT
1-3. Hasta aproximadamente 1 año
4. Momento basal a 1 año
5. En los días 1, 8, 15 del Ciclo 1
6. En los días 1, 5 del ciclo 3
7. En los días 1, 8 del Ciclo 1; el día 5 del Ciclo 3 y al EOT
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Tolerability and anti-tumor activity
Tolerabilidad y actividad anti-tumoral
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) Yes
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other Yes
E.7.1.3.1Other trial type description
A phase I/II trial to evaluate glofitamab in combination with chemotherapy in pediatric patients
Ensayo de fase I/II para evaluar glofitamab en combinación con quimioterapia en pacientes pediátrico
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial1
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned2
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA10
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Australia
China
Denmark
France
Germany
Italy
Korea, Republic of
Spain
United States
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
LVLS
UVUP
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years5
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years5
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 55
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) Yes
F.1.1.4.1Number of subjects for this age range: 10
F.1.1.5Children (2-11years) Yes
F.1.1.5.1Number of subjects for this age range: 28
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 17
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 10
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally Yes
F.3.3.6.1Details of subjects incapable of giving consent
Participants age 6 months to < 18 years at the time of signing Informed Consent for Part 1 and Cohort B of the study, and age 6 months to </= 30 years old at the time of signing
Informed Consent for Part 2 of the study
Participantes de 6 meses a < 18 años en el momento de firmar el Consentimiento informado para la Parte 1 y la Cohorte B del estudio, y de 6 meses a </= 30 años en el momento de la firma consentimiento informado para la Parte 2 del estudio
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state5
F.4.2 For a multinational trial
F.4.2.1In the EEA 25
F.4.2.2In the whole clinical trial 65
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Currently, the Sponsor does not have any plans to provide Roche glofitamab, obinutuzumab, and tocilizumab or any other study treatments to participants who have completed the study. The Sponsor may evaluate whether to continue providing glofitamab, obinutuzumab, and tocilizumab in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, available at the following
website:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
Actualmente, el Promotor no tiene planes para proporcionar glofitamab, obinutuzumab y tocilizumab de Roche ni ningún otro tratamiento del estudio a los participantes que hayan completado el estudio. El Promotor puede evaluar si continúa proporcionando glofitamab, obinutuzumab y tocilizumab de acuerdo con la Política Global de Roche sobre el Acceso Continuo al Medicamento en Investigación, disponible en el sitio web: http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-09-27
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-09-27
P. End of Trial
P.End of Trial StatusOngoing